Regression in cutaneous melanoma: histological assessment, immune mechanisms and clinical implications

Tumour regression is an immunologically driven process that results in complete or partial disappearance of tumour cells. This can be observed in histological sections as replacement of tumour cells with fibrosis, angiogenesis, and a variable inflammatory infiltrate. In primary cutaneous melanoma, the prognostic significance of regression has been debated for decades, in part because inconsistent histological criteria are used in prognostication studies. It is broadly accepted that CD8+ T lymphocytes are the primary effectors of the anti-tumour response, but the interplay between melanoma and the immune system is complex, dynamic, and incompletely understood. Sustained progress in unravelling the pathogenesis of melanoma regression has led to the identification of therapeutic targets, culminating in the development of immune checkpoint inhibitors for the management of advanced disease. Modern techniques allow for high-resolution spatial analyses of the tumour microenvironment. Such studies may lead to better understanding of the immune drivers of melanoma regression, thereby facilitating the search for new prognostic and predictive biomarkers to assist clinical decision-making.